BCL-2 inhibitors
Drugs that switch off BCL-2, the protein that lets cancer cells refuse to die; venetoclax transformed treatment of chronic lymphocytic leukaemia and acute myeloid leukaemia.
Overview
BCL-2 blocks the mitochondrial pathway of apoptosis. Venetoclax, a BH3 mimetic approved in 2016, produces deep remissions in chronic lymphocytic leukaemia in fixed-duration combinations with obinutuzumab or BTK inhibitors, and with azacitidine it became standard for older patients with acute myeloid leukaemia. Second-generation inhibitors such as sonrotoclax aim for greater selectivity, and BCL-XL and MCL-1 inhibitors target the related proteins that mediate resistance.
How it works
Small molecules mimic BH3-only proteins, binding BCL-2's groove so that BAX and BAK are released to trigger mitochondrial apoptosis.
- Deep, durable responses and fixed-duration treatment in CLL
- Standard of care in unfit AML
- Oral
- Tumour lysis syndrome requires ramp-up
- Neutropenia
- Resistance through BCL-2 mutation or MCL-1 upregulation
Latest papers
topQuery for this technology: (TITLE:"BCL-2 inhibitors" OR ABSTRACT:"BCL-2 inhibitors") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about BCL-2 inhibitors, not a curated reading list.
Similar pages
not linked directly; found by shared links- PersonPeter Hillmen
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